PURPOSE: Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated. METHODS: The pHstat technique was used to measure the lipolysis by recombinant dog gastric lipase (rDGL) of eight LBFs containing either medium (MC) or long (LC) chain triglycerides and a range of surfactants, at various pH values [1.5 to 7] representative of gastric and small intestine contents under both fasting and fed conditions. RESULTS: All LBFs were hydrolyzed by rDGL. The highest specific activities were measured at pH 4 with the type II and IIIA MC formulations that contained Tween®85 or Cremophor EL respectively. The maximum activity on LC formulations was recorded at pH 5 for the type IIIA-LC formulation. Direct measurement of LBF lipolysis using the pHstat, however, was limited by poor LC fatty acid ionization at low pH. CONCLUSIONS: Since gastric lipase initiates lipid digestion in the stomach, remains active in the intestine and acts on all representative LBFs, its implementation in future standardized in vitro assays may be beneficial. At this stage, however, routine use remains technically challenging.
PURPOSE:Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated. METHODS: The pHstat technique was used to measure the lipolysis by recombinant doggastric lipase (rDGL) of eight LBFs containing either medium (MC) or long (LC) chain triglycerides and a range of surfactants, at various pH values [1.5 to 7] representative of gastric and small intestine contents under both fasting and fed conditions. RESULTS: All LBFs were hydrolyzed by rDGL. The highest specific activities were measured at pH 4 with the type II and IIIA MC formulations that contained Tween®85 or Cremophor EL respectively. The maximum activity on LC formulations was recorded at pH 5 for the type IIIA-LC formulation. Direct measurement of LBF lipolysis using the pHstat, however, was limited by poor LC fatty acid ionization at low pH. CONCLUSIONS: Since gastric lipase initiates lipid digestion in the stomach, remains active in the intestine and acts on all representative LBFs, its implementation in future standardized in vitro assays may be beneficial. At this stage, however, routine use remains technically challenging.
Authors: Matthew F Crum; Natalie L Trevaskis; Hywel D Williams; Colin W Pouton; Christopher J H Porter Journal: Pharm Res Date: 2015-12-24 Impact factor: 4.200
Authors: André Brodkorb; Lotti Egger; Marie Alminger; Paula Alvito; Ricardo Assunção; Simon Ballance; Torsten Bohn; Claire Bourlieu-Lacanal; Rachel Boutrou; Frédéric Carrière; Alfonso Clemente; Milena Corredig; Didier Dupont; Claire Dufour; Cathrina Edwards; Matt Golding; Sibel Karakaya; Bente Kirkhus; Steven Le Feunteun; Uri Lesmes; Adam Macierzanka; Alan R Mackie; Carla Martins; Sébastien Marze; David Julian McClements; Olivia Ménard; Mans Minekus; Reto Portmann; Cláudia N Santos; Isabelle Souchon; R Paul Singh; Gerd E Vegarud; Martin S J Wickham; Werner Weitschies; Isidra Recio Journal: Nat Protoc Date: 2019-03-18 Impact factor: 13.491
Authors: Andrea Fratter; Vera Mason; Marzia Pellizzato; Stefano Valier; Arrigo Francesco Giuseppe Cicero; Erik Tedesco; Elisa Meneghetti; Federico Benetti Journal: Int J Mol Sci Date: 2019-02-04 Impact factor: 5.923